Background Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is the preferred operation for patients with chronic ulcerative colitis (CUC) refractory to medical therapy. Infliximab (IFX), ...an antitumor necrosis factor−α antibody, has demonstrated efficacy in medical management of CUC. The aim of this study is to determine if IFX before IPAA impacts short-term outcomes. Study Design A prospective institutional database was retrospectively reviewed for short-term complications after IPAA for CUC. Postoperative outcomes were compared between patients who received pre-IPAA IFX and those who did not. Results Between 2002 and 2005, 47 patients received IFX before IPAA, and 254 patients received none. There were no gender (p = 0.16) or body mass index (p = 0.07) differences between groups. IFX patients were younger than non-IFX patients (mean age 28.1 to 39.3 years) (p < 0.001). In IFX patients, 70% were receiving preoperative IFX, azathioprine, and corticosteroids. Mortality was nil. Overall surgical morbidity was similar: 61.7% and 48.8%, IFX and non-IFX, respectively (p = 0.10). Anastomotic leaks (p = 0.02), pouch-specific (p = 0.01) and infectious (p < 0.01) complications were more common in IFX patients. Multivariable analysis revealed IFX as the only factor independently associated with infectious complications (odds ratio OR = 3.5; CI, 1.6−7.5). In a separate analysis, incorporating age, high-dose corticosteroids, azathioprine, and severity of colitis, IFX remained significantly associated with infectious complications (OR = 2.7; CI, 1.1−6.7). Conclusions CUC patients treated with IFX before IPAA have substantially increased the odds of postoperative pouch-related and infectious complications. Additional prospective studies are required to determine if IFX alone or other factors contribute to the observed increases in infectious complications.
Introduction
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an established treatment for pseudomyxoma peritonei (PMP) from perforated low-grade appendiceal ...mucinous neoplasms (LAMN II). In a selected group of LAMN II patients without established PMP, CRS/HIPEC can be performed laparoscopically (L-CRS/HIPEC); however the short-term benefits and safety of this approach have yet to be determined. This study aims to determine the short-term outcomes from a series of L-CRS/HIPEC LAMN II patients compared to those who have undergone a similar open operation (O-CRS/HIPEC) for low-volume PMP.
Methods
LAMN II patients undergoing L-CRS/HIPEC at a UK national peritoneal tumour centre were compared to O-CRS/HIPEC patients (peritoneal cancer index ≤ 7). Outcomes of interest included Clavien–Dindo complication grade, operative time, blood transfusions, high dependency unit (HDU) admission, length of hospital stay, and histopathological findings.
Results
55 L-CRS/HIPEC were compared to 29 O-CRS/HIPEC patients (2003–2017). Groups were matched for age, sex, and procedures. Median operative time was 8.8 (IQR 8.1–9.5) h for L-CRS/HIPEC versus 7.3 (IQR 6.7–8) h for O-CRS/HIPEC (Mann–Whitney test
p
< 0.001). Post-operative HDU admission was 56% versus 97% (OR 0.04 95% CI 0.01–0.34) and median length of stay = 6 (IQR 5–8) versus 10 (IQR 8–11) days (
p
< 0.001) for L- versus O-CRS/HIPEC. Despite a normal pre-operative CT scan, 13/55 (23.6%) L-CRS/HIPEC patients had acellular mucin and 2/55 (3.5%) had mucin with epithelium present in their specimens. Residual appendix tumour was identified in 2/55 patients (3.6%). Clavien–Dindo Grade 1–4 complications were similar in both groups with no mortality.
Conclusion
L-CRS/HIPEC for LAMN II takes longer; however patients have significantly reduced length of HDU and overall stay, without increased post-operative complications. A significant proportion of LAMN II patients undergoing L-CRS/HIPEC have extra-appendiceal acellular mucin with some cases demonstrating residual cellular epithelium from the LAMN II. The risk of these patients developing PMP without surgery is under current review.
BACKGROUND:Appendix adenocarcinomas are rare tumors with propensity for peritoneal metastasis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an established treatment with ...curative intent, but, to date, studies reporting survival have been heterogeneous with regard to their patient groups (including other tumor types), interventions (not all patients receiving intraperitoneal chemotherapy), and follow-up (varying surveillance protocols).
OBJECTIVE:The aim of this study is to quantify the impact of this intervention on survival in a homogeneous group of patients with appendix adenocarcinoma receiving standardized treatment and follow-up, and to determine the impact of prognostic indicators on survival.
DESIGN:This is a retrospective analysis of a prospective database at a national peritoneal tumor center where all patients had their appendix pathology reviewed and management planned by a specialized peritoneal tumor multidisciplinary team.
MAIN OUTCOME MEASURES:Data were extracted on prognostic indicators including peritoneal cancer index, completeness of cytoreduction score, preoperative tumor markers, and histological features. Overall and disease event-free survival from the date of intervention were evaluated using Kaplan Meier curves and univariate Cox proportional hazards regression analysis.
RESULTS:A total of 65 patients underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for appendix adenocarcinoma between 2005 and 2015. Median follow-up was 44.3 months. The overall survival was 55.5% and disease event-free survival was 36.1% (5-year rate). Peritoneal Cancer Index <7, complete cytoreduction score of 0, and preoperative CEA of <6 were all associated with significantly higher overall and disease event-free survival. CA19-9 <38 and CA125 <31 were not associated with a significantly higher overall or disease event-free survival.
LIMITATIONS:The sample size was limited because of the rarity of this tumor type.
CONCLUSIONS:This study quantifies the impact of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy on overall and disease event-free survival for appendix adenocarcinoma, identifying key prognostic indicators that may guide treatment. It supports the referral of these rare tumors to specialist centers with appropriate expertise for initial management and follow-up. See Video Abstract at http://www.links.lww.com/DCR/A595.
Traditionally patients with colorectal peritoneal metastases (CRPM) were offered palliative chemotherapy and best supportive care. With the introduction of cytoreductive surgery (CRS) and ...hyperthermic intraperitoneal chemotherapy (HIPEC), patients in the UK have been referred to nationally approved centres. This study describes the pattern of referral and outcomes of patients managed through one UK centre.
and Methods: A prospective register recorded referrals, demographics, prior treatment pathways, and specialist multidisciplinary team (MDT) decisions (2002-2015). Peritoneal cancer index (PCI) was recorded intra-operatively; complete cytoreduction was deemed when a CC0/1 was achieved. Complications were classified using NCI CTCAE. v.4. Median overall survivals (OS) were described for those treated by CRS/HIPEC and in derived estimates for patients with isolated peritoneal metastases treated by chemotherapy alone in the ARCAD trials consortium.
Two-hundred-eighty-six patients with CRPM were referred. Despite increasing numbers of referrals annually, the proportion of patients selected for CRS/HIPEC decreased from 64.5%, to 40%, and to 37.1% for 2002–09, 2010–12, and 2013–15, respectively (p < 0.017). CRS/HIPEC was undertaken in 117 patients with a median PCI of 7 and CC0/1 achieved in 86.3%. NCI CTCAE grade 3/4 complication rates were 9.4%; 30-day mortality was 0.85%. Median OS following CRS/HIPEC was 46.0 months: that for patients not receiving CRS/HIPEC was 13.2 months.
The evolution of the national peritoneal treatment centre over 14 years has been associated with increased referral numbers, refinement of selection for major surgery, matched with achievements of low complication rates and survival advantages in selected patients compared with traditional non-surgical treatments.
Need to search for edible plants with antimicrobial and nutraceutical properties is increasing due to reduced efficacy, high cost and increased resistance of conventional medicine and for food ...quality and safety applications. This study analysed proximate, amino acids, minerals, secondary metabolites, and phytochemical composition of Moringa oleifera from two geographical locations in India and there was wide variation between two regions. Proximate composition revealed high protein, fibre and less fat content of leaves. Glutamate, arginine and isoleucine were the major amino acids. Calcium and potassium was found to be high in leaves and copper was high in seeds. Leaves and seeds had high vitamin E and C. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed 185 compounds from seeds and 50 compounds from leaves. 1,30-triacontanediol, octacosane, Z-14-nonacosane were found to be major compounds of leaves from Madurai and nonacosane, .gamma.-sitosterol were found to be major compounds of leaves from Chennai. 6-octadecenoic acid, n-hexadecanoic acid, oleic acid were found to be major compounds of seeds from Madurai and 13-docosenamide, (Z)-, propionamide, ethyl oleate were found to be major compounds of seeds from Chennai. Leaves had high total polyphenols and antioxidant activity. High antimicrobial activity against dysentery causing entero-pathogens was found in leaves and seeds from Madurai.
Background
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are an established treatment for pseudomyxoma peritonei (PMP), but it is a major surgical procedure and ...may be associated with long-term morbidity. To date, health-related quality-of-life (HRQL) data among survivors are lacking.
Methods
A two-period qualitative study investigated patients undergoing CRS-HIPEC for PMP at a national peritoneal tumor center between 2003 and 2011. First, the European Organization for Research and Treatment (EORTC)-QLQ C30 HRQL questionnaire was used longitudinally preoperatively and at postoperative months 3, 6, 9, 12, 18, and 24, then yearly thereafter. Second, it was updated in 2016 as a cross-sectional study. Both studies were compared with age- and sex-matched reference populations (one-way
t
tests).
Results
A total of 553 longitudinal HRQL questionnaires were completed for 137 patients, truncated at 60 months. In the 2016 update, 85 responses were received from 103 survivors (mean follow-up period, 8.11 years). Patients’ physical, role, and social function scores were impaired until 12 months postoperatively, after which the scores did not differ significantly from those of with reference populations. Similarly, fatigue, appetite loss, insomnia, and financial difficulties worsened significantly compared with reference populations in the first 12-months and then normalized. In contrast, impaired cognitive function (82.3 vs 88.5;
P
= 0.017), constipation (13.7 vs 7.3;
P
= 0.032), and diarrheal symptoms (15.1 vs 4.9;
P
= 0.0006) persisted through both periods. Global health scores did not differ significantly from those of the reference population.
Conclusions
Beyond 12 months postoperatively, CRS-HIPEC for PMP is associated with a good quality of life except for some cognitive functional impairment and bowel disturbances.
Inactivation of the DNA mismatch repair pathway manifests as microsatellite instability, an accumulation of mutations that drives carcinogenesis. Here, we determined whether microsatellite ...instability in acute myeloid leukemia and myelodysplastic syndrome correlated with chromosomal instability and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity through disruption of DNA repair function. Acute myeloid leukemia cell lines (n=12) and primary cell samples (n=18), and bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients (n=63) were profiled for microsatellite instability using fluorescent fragment polymerase chain reaction. PARP inhibitor sensitivity was performed using cell survival, annexin V staining and cell cycle analysis. Homologous recombination was studied using immunocytochemical analysis. SNP karyotyping was used to study chromosomal instability. RNA silencing, Western blotting and gene expression analysis was used to study the functional consequences of mutations. Acute myeloid leukemia cell lines (4 of 12, 33%) and primary samples (2 of 18, 11%) exhibited microsatellite instability with mono-allelic mutations in CtIP and MRE11. These changes were associated with reduced expression of mismatch repair pathway components, MSH2, MSH6 and MLH1. Both microsatellite instability positive primary acute myeloid leukemia samples and cell lines demonstrated a downregulation of homologous recombination DNA repair conferring marked sensitivity to PARP inhibitors. Similarly, bone marrow mononuclear cells from 11 of 56 (20%) patients with de novo high-risk myelodysplastic syndrome exhibited microsatellite instability. Significantly, all 11 patients with microsatellite instability had cytogenetic abnormalities with 4 of them (36%) possessing a mono-allelic microsatellite mutation in CtIP. Furthermore, 50% reduction in CtIP expression by RNA silencing also down-regulated homologous recombination DNA repair responses conferring PARP inhibitor sensitivity, whilst CtIP differentially regulated the expression of homologous recombination modulating RecQ helicases, WRN and BLM. In conclusion, microsatellite instability dependent mutations in DNA repair genes, CtIP and MRE11 are detected in myeloid malignancies conferring hypersensitivity to PARP inhibitors. Microsatellite instability is significantly correlated with chromosomal instability in myeloid malignancies.
The use of natural coagulant protein in drinking water treatment has been discussed for a long time, though the method is still not in practice, probably due to limited knowledge and availability of ...material. In the present work, different Mustard varieties were tested for the presence of coagulant protein compared with Moringa seed extract and their potential application in water treatment. The coagulation activity of the protein extract was measured using synthetic clay solution as well as water from pond. The protein content was determined by Bradford method, molecular mass determined by Sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and peptide sequence was analyzed by Mass spectrometry. Extract of Mustard (large) and Moringa seed showed coagulation activity of ≅70 and ≅85 % after 90 min, respectively. Interestingly, seed extracts from other Mustard varieties had coagulation activity after heat activation at 95 °C for 5 h. However, the coagulation activity of Mustard seed extract against turbid pond water was higher (≅60 %) compared to Moringa seed extract (≅50 %). The peptide sequence analysis of 6.5 and 9 kDa proteins was found to be homologous to Moringa coagulant protein and napin3, respectively. To our knowledge, this could be the first report on Mustard seed having coagulant protein. The coagulation activity of Mustard (large) against highly turbid pond water suggested that it could be a potential natural coagulant for water treatment.
Mutations in dystrophin cause Duchenne muscular dystrophy (DMD), but absent dystrophin does not invariably cause necrosis in all muscles, life stages and species. Using DNA microarray, we established ...a molecular signature of dystrophinopathy in the mdx mouse, with evidence that secondary mechanisms are key contributors to pathogenesis. We used variability controls, adequate replicates and stringent analytic tools, including significance analysis of microarrays to estimate and manage false positive rates. In leg muscle, we identified 242 differentially expressed genes, >75% of which have not been previously reported as altered in human or animal dystrophies. Data provide evidence for coordinated activity of numerous components of a chronic inflammatory response, including cytokine and chemokine signaling, leukocyte adhesion and diapedesis, invasive cell type-specific markers, and complement system activation. Selective chemokine upregulation was confirmed by RT-PCR and immunoblot, and may be a key determinant of the nature of the inflammatory response in dystrophic muscle. Up-regulation of secreted phosphoprotein 1 (minopontin, osteopontin) mRNA and protein in dystrophic muscle identified a novel linkage between inflammatory cells and repair processes. Extracellular matrix genes were up-regulated in mdx to levels similar to those in DMD. Since, unlike DMD, mdx exhibits little fibrosis, data suggest that collagen regulation at post-transcriptional stages mediates extensive fibrosis in DMD. Taken together, these data identify a relatively neglected aspect of DMD, suggest new treatment avenues, and highlight the value of genome-wide profiling in study of complex disease processes.
PDF
